RESUMEN
We investigated the effects of 4% fructose plus moderately high salt (MHS) (4% NaCl) treatment on tissue aldehyde conjugates, platelet cytosolic free calcium ([Ca2+]i), renal morphology, and systolic blood pressure (SBP) in Wistar-Kyoto rats, and whether these effects were reversible (R) after withdrawal of treatment. At age 7 weeks, rats were divided into 4 groups: NS group, given normal salt (NS) diet (0.7% NaCl) for 18 weeks; NS+F(R) group, NS diet and fructose in water for 14 weeks, then 4 weeks fructose withdrawal; MHS+F group, NS diet and fructose for 6 weeks, then MHS diet and fructose for 12 weeks; and MHS+F(R) group, NS diet and fructose for 6 weeks, then MHS diet and fructose for 8 weeks, then MHS and fructose withdrawal for 4 weeks. SBP in the NS+F(R) group increased during fructose treatment, but normalized within 1 week of withdrawal. Tissue aldehyde conjugates and platelet [Ca2+]i were normal at completion. Adverse renal vascular changes did not reverse to normal and were similar to those of the salt plus fructose-treated groups. This may have implications for future development of hypertension. MHS did not cause any additional increase in SBP or associated tissue alterations when added to fructose treatment. However, the SBP and tissue changes persisted even after discontinuation of treatment. The fructose and salt combination may result in long-lasting vascular alterations leading to hypertension.
Asunto(s)
Fructosa , Hipertensión/inducido químicamente , Riñón/efectos de los fármacos , Cloruro de Sodio Dietético/farmacología , Aldehídos/metabolismo , Animales , Aorta/efectos de los fármacos , Aorta/metabolismo , Presión Sanguínea/efectos de los fármacos , Calcio/metabolismo , Corazón/anatomía & histología , Corazón/efectos de los fármacos , Hipertensión/metabolismo , Hipertensión/patología , Hipertensión/fisiopatología , Riñón/metabolismo , Riñón/patología , Hígado/anatomía & histología , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratas , Ratas Endogámicas WKYRESUMEN
BACKGROUND: Approximately one-half of hypertensive individuals are salt sensitive, and animal models of human hypertension also exhibit increased blood pressure when exposed to high-salt diets. Salt sensitivity is associated with insulin resistance, which results in altered glucose metabolism, increasing aldehydes. Previously, the authors have shown that a high-salt diet (8% NaCl) caused an increase in blood pressure, tissue aldehyde conjugates and cytosolic free calcium, with resulting adverse renal vascular changes, in Wistar-Kyoto rats. Treatment with lipoic acid (LA) prevented an increase in blood pressure and attenuated biochemical and histopathological changes. OBJECTIVES: The objective of the present study was to investigate the effect of a moderately high-salt (MHS) diet (4% NaCl) on these same parameters, and the modulating effect of LA in Wistar-Kyoto rats. METHODS: At seven weeks of age, animals were divided into three groups. The normal-salt group was given a diet containing 0.7% NaCl; the MHS group was given a diet containing 4% NaCl; and the MHS+LA group was given a diet containing 4% NaCl plus LA (500 mg/kg diet) for 10 weeks. RESULTS: At the end of the study, animals in the MHS group did not show any increase in systolic blood pressure, platelet cytosolic free calcium and tissue aldehyde conjugates. Furthermore, there were no adverse effects in renal vascular morphology compared with the normal salt group. In the MHS+LA group, LA did not lower blood pressure or affect other biochemical and histopathological parameters. CONCLUSION: The present study suggests that moderately high sodium intake, over a short period, may not have any adverse effect and that LA does not lower blood pressure in normotensive rats.
RESUMEN
Low alcohol intake in humans lowers the risk of coronary heart disease and may lower blood pressure. In hypertension, insulin resistance with altered glucose metabolism leads to increased formation of aldehydes. We have shown that chronic low alcohol intake decreased systolic blood pressure (SBP) and tissue aldehyde conjugates in spontaneously hypertensive rats and demonstrated a strong link between elevated tissue aldehyde conjugates and hypertension in salt-induced hypertensive Wistar-Kyoto (WKY) rats. This study investigated the antihypertensive effect of chronic low alcohol consumption in high salt-treated WKY rats and its effect on tissue aldehyde conjugates, platelet cytosolic free calcium ([Ca2+]i, and renal vascular changes. Animals, aged 7 weeks, were divided into three groups of six animals each. The control group was given normal salt diet (0.7% NaCl) and regular drinking water; the high salt group was given a high salt diet (8% NaCl) and regular drinking water; the high salt + ethanol group was given a high salt diet and 0.25% ethanol in drinking water. After 10 weeks, SBP, platelet [Ca2+]i, and tissue aldehyde conjugates were significantly higher in rats in the high salt group as compared with controls. Animals on high salt diets also showed smooth muscle cell hyperplasia in the small arteries and arterioles of the kidney. Ethanol supplementation prevented the increase in SBP and platelet [Ca2+]i and aldehyde conjugates in liver and aorta. Kidney aldehyde conjugates and renal vascular changes were attenuated. These results suggest that chronic low ethanol intake prevents salt-induced hypertension and attenuates renal vascular changes in WKY rats by preventing an increase in tissue aldehyde conjugates and cytosolic [Ca2+]i.
Asunto(s)
Etanol/farmacología , Hipertensión/prevención & control , Cloruro de Sodio/efectos adversos , Aldehídos/análisis , Animales , Plaquetas/química , Calcio/análisis , Relación Dosis-Respuesta a Droga , Etanol/administración & dosificación , Hipertensión/inducido químicamente , Hipertensión/tratamiento farmacológico , Riñón/irrigación sanguínea , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/patología , Ratas , Ratas Endogámicas WKY , Cloruro de Sodio/administración & dosificaciónRESUMEN
There is strong evidence that excess dietary salt (NaCl) is a major factor contributing to the development of hypertension. Salt sensitive humans and rats develop hypertension even on a normal salt diet. Salt sensitivity is associated with glucose intolerance and insulin resistance in both humans and animal models, including Dahl salt sensitive (DSS) rats. In insulin resistance, impaired glucose metabolism leads to elevated endogenous aldehydes. These aldehydes bind sulfhydryl groups of membrane proteins, altering calcium channels, increasing cytosolic free calcium ([Ca2+]i) and blood pressure. Treatment with lipoic acid, an endogenous sulfur-containing fatty acid, normalizes insulin resistance and lowers tissue aldehyde conjugates, cytosolic [Ca2+]i, and blood pressure in spontaneously hypertensive rats (SHR). The objective of this study was to investigate the effects of a normal salt diet on tissue aldehyde conjugates, cytosolic [Ca2+]i and blood pressure in DSS rats and to determine whether lipoic acid supplementation prevents the increase in blood pressure and biochemical changes. Starting at 7 weeks of age, DSS rats were divided into three groups of six animals each and treated for 6 weeks with diets as follows: DSS-low salt, 0.4% NaCl; DSS-normal salt, 0.7% NaCl, and; DSS-normal salt + lipoic acid, 0.7% NaCl + lipoic acid 500 mg/kg feed. At completion, animals in the normal salt group had elevated systolic blood pressure, cytosolic [Ca2+]i and tissue aldehyde conjugates as compared to the low salt group. They also showed smooth muscle cell hyperplasia in small arteries and arterioles of the kidney. Dietary lipoic acid supplementation attenuated the increase in systolic blood pressure and associated biochemical and histopathological changes.
Asunto(s)
Suplementos Dietéticos , Hipertensión/dietoterapia , Hipertensión/prevención & control , Hígado/crecimiento & desarrollo , Cloruro de Sodio Dietético/farmacología , Ácido Tióctico/farmacología , Aldehídos/análisis , Aldehídos/metabolismo , Animales , Antioxidantes/farmacología , Glucemia/metabolismo , Plaquetas/química , Presión Sanguínea/efectos de los fármacos , Calcio/sangre , Insulina/sangre , Resistencia a la Insulina/genética , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Endogámicas Dahl , Ratas Endogámicas SHR , Ácido Tióctico/metabolismo , Factores de TiempoRESUMEN
There is strong evidence that excess dietary salt (NaCl) is a major factor contributing to the development of hypertension. Salt-sensitive humans and rats develop hypertension even on a normal-salt diet. Salt sensitivity is associated with glucose intolerance and insulin resistance in both humans and animal models, including Dahl salt-sensitive (DSS) rats. In insulin resistance, impaired glucose metabolism leads to elevated endogenous aldehydes that bind sulfhydryl groups of membrane proteins, altering calcium channels, and increasing cytosolic free calcium ([Ca2+]i) and blood pressure. Vitamin E lowers tissue aldehyde conjugates, cytosolic [Ca2+]i, and blood pressure in spontaneously hypertensive rats and fructose-induced hypertensive Wistar Kyoto rats, models of insulin resistance. This study investigated the effect of a normal-salt diet on tissue aldehyde conjugates, cytosolic [Ca2+]i, and blood pressure in DSS rats and the effect of vitamin E supplementation on blood pressure and associated biochemical changes in these animals. Seven-week-old DSS rats were divided into 3 groups of 6 animals each and treated for 6 weeks with diets as follows: low-salt (0.4% NaCl); normal-salt (0.7% NaCl) and normal salt (0.7% NaCl) plus vitamin E (34 mg/kg feed). At completion, animals in the normal-salt group had significantly elevated systolic blood pressure, cytosolic [Ca2+]i, and tissue aldehyde conjugates compared with the low-salt group. They also showed smooth muscle cell hyperplasia in small arteries and arterioles of the kidney. Dietary vitamin E supplementation significantly attenuated the increase in systolic blood pressure and associated biochemical and histopathologic changes.
Asunto(s)
Antioxidantes/farmacología , Suplementos Dietéticos , Hipertensión/tratamiento farmacológico , Vitamina E/farmacología , Aldehídos/metabolismo , Animales , Antioxidantes/uso terapéutico , Plaquetas/efectos de los fármacos , Plaquetas/metabolismo , Presión Sanguínea/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Calcio/metabolismo , Modelos Animales de Enfermedad , Ingestión de Alimentos/efectos de los fármacos , Hipertensión/patología , Hipertensión/fisiopatología , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Endogámicas Dahl , Vitamina E/uso terapéuticoRESUMEN
There is strong evidence that points to excess dietary salt as a major factor contributing to the development of hypertension. Salt sensitivity is associated with glucose intolerance and insulin resistance in both animal models and humans. In insulin resistance, impaired glucose metabolism leads to elevated endogenous aldehydes which bind to vascular calcium channels, increasing cytosolic [Ca2+]i and blood pressure. In an insulin resistant animal model of hypertension, spontaneously hypertensive rats (SHRs), dietary supplementation with lipoic acid lowers tissue aldehydes and plasma insulin levels and normalizes blood pressure. The objective of this study is to examine the effects of a high salt diet on tissue aldehydes, cytosolic [Ca2+]i and blood pressure in WKY rats and to investigate whether dietary supplementation with lipoic acid can prevent a salt induced increase in blood pressure. Starting at 7 weeks of age, WKY rats were divided into three groups of six animals each and treated for 10 weeks with diets as follows: WKY-normal salt (0.7% NaCl); WKY-high salt (8% NaCl); WKY-high salt + lipoic acid (8% NaCl diet + lipoic acid 500 mg/Kg feed). At completion, animals in the high salt group had elevated systolic blood pressure, platelet [Ca2+]i, and tissue aldehyde conjugates compared with the normal salt group and showed smooth muscle cell hyperplasia in the small arteries and arterioles of the kidneys. Dietary alpha-lipoic acid supplementation in high salt-treated WKY rats normalized systolic blood pressure and cytosolic [Ca2+]i and aldehydes in liver and aorta. Kidney aldehydes and renal vascular changes were attenuated, but not normalized.